Brief post-hypoxic-ischemic hypothermia markedly delays neonatal brain injury

The influence of post-insult temperature modulation on ischemic injury in immature brain was studied in 7-day-old rats that underwent a unilateral carotid artery ligation followed by exposure to hypoxia in 8% oxygen at an ambient temperature of 36.5°C. After the hypoxic exposure, the animals were separated into three groups and placed for 3 h in temperature-controlled incubators set at 32°C, 35°C, and 38°C. In Study 1, the influence of post-insult temperature modulation was assessed after graded cerebral hypoxic-ischemic injury. Brain damage was assessed 1 week after the insult by comparison of wet weights in the cerebral hemispheres ipsilateral and contralateral to the carotid artery ligation. Rectal temperatures of the animals significantly correlated with extent of brain injury after 60 min (Spearman correlation coefficient, ρ = 0.44, ρ = 0.005) and 90 min (ρ = 0.46, P = 0.004) but not 120 min of hypoxia (ρ = 0.18, P = 0.46). In Study 2, animals were exposed to 75 min hypoxia, and injury was assessed morphometrically and histologically at 1 and 4 weeks after the injury. Rectal temperatures significantly correlated with the extent of ischemic injury in the cerebral cortex (ρ = 0.3, P = 0.046) and striatum (ρ = 0.3, P = 0.048) at 1 week, but not 3 weeks, after the insult. The findings indicate that post-insult hypothermia delayed the expression of mild to moderate brain damage by more than a week, after which the damage was as severe as in normothermic animals. The results indicate that the events that determine the final expression of a neonatal hypoxic-ischemic insult can be extended over a long interval by post-insult hypothermia.